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Edited by Richard E. Lenski, Michigan State University, East Lansing, MI, and approved April 18, 2013 (received for review March 28, 2013)
Abstract
Mucosal surfaces are a main entry point for pathogens and the principal sites of defense against infection. Both bacteria and phage are associated with this mucus. Here we show that phage-to-bacteria ratios were increased, relative to the adjacent environment, on all mucosal surfaces sampled, ranging from cnidarians to humans. In vitro studies of tissue culture cells with and without surface mucus demonstrated that this increase in phage abundance is mucus dependent and protects the underlying epithelium from bacterial infection. Enrichment of phage in mucus occurs via binding interactions between mucin glycoproteins and Ig-like protein domains exposed on phage capsids. In particular, phage Ig-like domains bind variable glycan residues that coat the mucin glycoprotein component of mucus. Metagenomic analysis found these Ig-like proteins present in the phages sampled from many environments, particularly from locations adjacent to mucosal surfaces. Based on these observations, we present the bacteriophage adherence to mucus model that provides a ubiquitous, but non–host-derived, immunity applicable to mucosal surfaces. The model suggests that metazoan mucosal surfaces and phage coevolve to maintain phage adherence. This benefits the metazoan host by limiting mucosal bacteria, and benefits the phage through more frequent interactions with bacterial hosts. The relationships shown here suggest a symbiotic relationship between phage and metazoan hosts that provides a previously unrecognized antimicrobial defense that actively protects mucosal surfaces.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: jeremybarr85{at}gmail.com.
Author contributions: J.J.B. and F.R. designed research; J.J.B., R.A., K.L.W., M.L.E., J.P., A.S.C., and P.S. performed research; J.J.B., K.L.W., M.L.E., J.P., A.S., R.W., A.S.C., and K.S.D. contributed new reagents/analytic tools; J.J.B., R.A., M.F., K.L.W., A.S., R.W., P.S., M.Y., and F.R. analyzed data; and J.J.B., M.Y., and F.R. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
See Commentary on page 10475.
Data deposition: Raw glycan array data are available from the Consortium for Functional Glycomics (accession no. 2621).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1305923110/-/DCSupplemental.
Freely available online through the PNAS open access option.
- Jeremy J. Barra,1,
- Rita Auroa,
- Mike Furlana,
- Katrine L. Whitesona,
- Marcella L. Erbb,
- Joe Poglianob,
- Aleksandr Stotlanda,
- Roland Wolkowicza,
- Andrew S. Cuttinga,
- Kelly S. Dorana,
- Peter Salamonc,
- Merry Youled, and
- Forest Rohwera
- aDepartment of Biology, San Diego State University, San Diego, CA 92182;
- bDivision of Biological Sciences, University of California, San Diego, CA 92093;
- cDepartment of Mathematics and Statistics, San Diego State University, San Diego, CA 92182; and
- dRainbow Rock, Ocean View, HI 96737
Edited by Richard E. Lenski, Michigan State University, East Lansing, MI, and approved April 18, 2013 (received for review March 28, 2013)
Abstract
Mucosal surfaces are a main entry point for pathogens and the principal sites of defense against infection. Both bacteria and phage are associated with this mucus. Here we show that phage-to-bacteria ratios were increased, relative to the adjacent environment, on all mucosal surfaces sampled, ranging from cnidarians to humans. In vitro studies of tissue culture cells with and without surface mucus demonstrated that this increase in phage abundance is mucus dependent and protects the underlying epithelium from bacterial infection. Enrichment of phage in mucus occurs via binding interactions between mucin glycoproteins and Ig-like protein domains exposed on phage capsids. In particular, phage Ig-like domains bind variable glycan residues that coat the mucin glycoprotein component of mucus. Metagenomic analysis found these Ig-like proteins present in the phages sampled from many environments, particularly from locations adjacent to mucosal surfaces. Based on these observations, we present the bacteriophage adherence to mucus model that provides a ubiquitous, but non–host-derived, immunity applicable to mucosal surfaces. The model suggests that metazoan mucosal surfaces and phage coevolve to maintain phage adherence. This benefits the metazoan host by limiting mucosal bacteria, and benefits the phage through more frequent interactions with bacterial hosts. The relationships shown here suggest a symbiotic relationship between phage and metazoan hosts that provides a previously unrecognized antimicrobial defense that actively protects mucosal surfaces.
- symbiosis
- host-pathogen
- virus
- immunoglobulin
- immune system
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: jeremybarr85{at}gmail.com.
Author contributions: J.J.B. and F.R. designed research; J.J.B., R.A., K.L.W., M.L.E., J.P., A.S.C., and P.S. performed research; J.J.B., K.L.W., M.L.E., J.P., A.S., R.W., A.S.C., and K.S.D. contributed new reagents/analytic tools; J.J.B., R.A., M.F., K.L.W., A.S., R.W., P.S., M.Y., and F.R. analyzed data; and J.J.B., M.Y., and F.R. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
See Commentary on page 10475.
Data deposition: Raw glycan array data are available from the Consortium for Functional Glycomics (accession no. 2621).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1305923110/-/DCSupplemental.
Freely available online through the PNAS open access option.
Bacteriophage on mucus provide immunity
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